The study investigates the impact of Alzheimer's disease (AD)-associated protein amyloid-β (Aβ) on human neural stem cells (NSCs). Aβ treatment significantly enhances senescence-related characteristics in NSCs, including increased expression of p16 and p21, upregulation of genes associated with the senescence-associated secretory phenotype (SASP), elevated SA-β-gal activity, and activation of the DNA damage response. Further analysis reveals that Aβ treatment downregulates SIRT1, a protein crucial for regulating the aging process, and decreases downstream targets PGC-1α and FOXO3. Overexpression of SIRT1 significantly alleviates Aβ-induced senescent markers in NSCs, suggesting that SIRT1 may be a promising therapeutic target for treating age-related neurodegenerative diseases, including AD. The findings highlight the role of Aβ in accelerating cellular senescence in NSCs and the potential of SIRT1 as a therapeutic target.The study investigates the impact of Alzheimer's disease (AD)-associated protein amyloid-β (Aβ) on human neural stem cells (NSCs). Aβ treatment significantly enhances senescence-related characteristics in NSCs, including increased expression of p16 and p21, upregulation of genes associated with the senescence-associated secretory phenotype (SASP), elevated SA-β-gal activity, and activation of the DNA damage response. Further analysis reveals that Aβ treatment downregulates SIRT1, a protein crucial for regulating the aging process, and decreases downstream targets PGC-1α and FOXO3. Overexpression of SIRT1 significantly alleviates Aβ-induced senescent markers in NSCs, suggesting that SIRT1 may be a promising therapeutic target for treating age-related neurodegenerative diseases, including AD. The findings highlight the role of Aβ in accelerating cellular senescence in NSCs and the potential of SIRT1 as a therapeutic target.